The proposed studies are designed to elucidate the role of genetic and environmental factors in the pathogenesis of porphyria cutanea tarda. The incidence of familial porphyria cutanea tarda in a large group of patients with this disease will be determined by measuring urinary uroporphyrin concentration, fecal isocoproporphyrin concentration, and red cell uroporphyrinogen decarboxylase activity in all the available first degree relatives of these patients. These values will be compared to our previously determined normal values, as well as those obtained in clinically non-porphyric subjects with alcoholic liver disease, subjects with hepatic siderosis, and all the available first degree relatives of these subjects. The effects of the chronic administration of alcohol on hepatic and red cell uroporphyrinogen decarboxylase activity will be studied in rats.